Similar Transcriptomic Alterations in Cx43 Knockdown and Knockout Astrocytes

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Abstract
Previous findings of widespread transcriptomic alteration in tissues from connexin null mice raise the issue of whether the transcriptomic changes are directly due to connexin down-regulation or to “compensatory” developmental alterations for the missing gene. To start addressing this question, the authors compared with wild-type control the gene expression profiles of connexin43 (Cx43) knockout and Cx43siRNA knockdown wild-type cortical astrocytes. Array analysis revealed remarkable parallelism of transcriptomic changes in knockout and knockdown astrocytes, with similarly altered genes being located on all chromosomes and encoding proteins involved in a wide diversity of cell functions. Moreover, gene expression variability was analogously higher in Cx43 null and siRNA-treated astrocytes, and expression interlinkages were similarly altered among a selected subset of genes. This highly significant overlap between transcriptomic alterations in Cx43 knockout and knockdown astrocytes suggests that the widespread changes more likely reflect connexin-dependent Gene Regulatory Networks rather than developmental compensation for the missing gene.